scholarly journals Antiepileptic Effect ofUncaria rhynchophyllaandRhynchophyllineInvolved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hsin-Cheng Hsu ◽  
Nou-Ying Tang ◽  
Chung-Hsiang Liu ◽  
Ching-Liang Hsieh
Keyword(s):  
Kainic Acid ◽  
Epileptic Seizures ◽  
Signal Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Signal Pathways ◽  
Sprague Dawley ◽  
Acute Seizures ◽  
Anticonvulsive Effect ◽  
Kinase Phosphorylation ◽  
Mapk Signal Pathway

Seizures cause inflammation of the central nervous system. The extent of the inflammation is related to the severity and recurrence of the seizures. Cell surface receptors are stimulated by stimulators such as kainic acid (KA), which causes intracellular mitogen-activated protein kinase (MAPK) signal pathway transmission to coordinate a response. It is known thatUncaria rhynchophylla(UR) andrhynchophylline(RP) have anticonvulsive effects, although the mechanisms remain unclear. Therefore, the purpose of this study is to develop a novel strategy for treating epilepsy by investigating how UR and RP initiate their anticonvulsive mechanisms. Sprague-Dawley rats were administered KA (12 mg/kg, i.p.) to induce seizure before being sacrificed. The brain was removed 3 h after KA administration. The results indicate that pretreatment with UR (1.0 g/kg), RP (0.25 mg/kg), and valproic acid (VA, 250 mg/kg) for 3 d could reduce epileptic seizures and could also reduce the expression of c-Jun aminoterminal kinase phosphorylation (JNKp) of MAPK signal pathways in the cerebral cortex and hippocampus brain tissues. Proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-αremain unchanged, indicating that the anticonvulsive effect of UR and RP is initially involved in the JNKp MAPK signal pathway during the KA-induced acute seizure period.

Uncaria rhynchophylla Upregulates the Expression of MIF and Cyclophilin A in Kainic Acid-Induced Epilepsy Rats: A Proteomic Analysis

2010 ◽  
Vol 38 (04) ◽  
pp. 745-759 ◽  
Author(s):  
Wan-Yu Lo ◽  
Fuu-Jen Tsai ◽  
Chung-Hsiang Liu ◽  
Nou-Ying Tang ◽  
Shan-Yu Su ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Kainic Acid ◽  
Chinese Herb ◽  
Cyclophilin A ◽  
Epileptic Seizures ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Western Blots ◽  
Uncaria Rhynchophylla ◽  
Anticonvulsive Effect

Uncaria rhynchophylla (Miq) Jack (UR) is a traditional Chinese herb and is used for the treatment of convulsive disorders, including epilepsy. Our previous study has shown that UR, as well as its major component rhynchophylline (RH), has an anticonvulsive effect and this effect is closely related to its scavenging activities of oxygen free radicals. The purpose of the present study was to investigate the effect of (UR) on the expression of proteins using a proteomics analysis in Sprague-Dawley (SD) rats with kainic acid (KA)-induced epileptic seizures. We profiled the differentially expressed proteins on two-dimensional electrophoresis (2-DE) maps derived from the frontal cortex and hippocampus of rat brain tissue 24 hours after KA-induced epileptic seizures. The results indicated that macrophage migration inhibitory factor (MIF) and cyclophilin A were under expressed in frontal cortex by an average of 0.19- and 0.23-fold, respectively. In the frontal cortex, MIF and cyclophilin A were significantly decreased in the KA group and these decreases were confirmed by the Western blots. However, in the hippocampus, only cyclophilin A was significantly decreased in the KA group. In addition, in real-time quantitative PCR (Q-PCR), MIF and cyclophilin A gene expressions were also significantly under expressed in the frontal cortex, and only the cyclophilin A gene was also significantly under expressed in the hippocampus in the KA group. These under expressions of MIF and cyclophilin A could be overcome by the treatment of UR and RH. In conclusion, the under expressions of MIF and cyclophilin A in the frontal cortex and hippocampus in KA-treated rats, which were overcome by both UR and UH treatment, suggesting that both MIF and cyclophilin A at least partly participate in the anticonvulsive effect of UR.

Differentially expressed circRNA and mRNA profiles of neural stem cells with radiation irradiation

2020 ◽  
Author(s):  
Zhaopeng Cai ◽  
Shan Wang ◽  
Zhongyu Xie ◽  
Peng Wang ◽  
Huiyong Shen ◽  
...  
Keyword(s):  
Regulatory Mechanism ◽  
Circular Rna ◽  
Signal Pathway ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Spine Metastasis ◽  
Radiation Induced ◽  
Differentially Expressed Mrna ◽  
Oncology Practice ◽  
Mapk Signal Pathway

Abstract Background Spine metastasis is common but highly problematic in clinical oncology practice. Radiotherapy plays an important role in the treatment of spine metastasis, but it at the same time damages the nervous tissue, especially the neural stem cell (NSC), and leads to radiation induced myelopathy. Circular RNA (circRNA) is a kind of non-coding RNA which responses to external stimulus and regulates cellular functions. However, the mechanism of radiotherapy affecting NSC and the role of circRNA in this process are still unclear. Methods The circRNA and mRNA of NSC treated with radiation or not were detect using next-generation sequencing. RT-PCR assays were preformed to confirm the sequencing results and the feature of differentially expressed circRNA. Bioinformation analyses were conducted to identified the critical circRNA and mRNA, as well as the enriched functions and pathways. Moreover, a circRNA-miRNA-mRNA network was constructed to investigate the possible regulatory mechanism. Results A total of 421 differentially expressed circRNA and 1602 differentially expressed mRNA of NSC were identified after radiotherapy. The GO and KEGG analysis of the differentially expressed mRNA as well as the host genes of the differentially expressed circRNA were performed and several key signal pathways such as MAPK signal pathway were identified. Moreover, a circRNA-miRNA-mRNA network focusing on MAPK signal pathway was shown and predicted that chr5:127160496|127165240 could be the critical circRNA in the regulatory mechanism of radiation treated NSCs. Conclusion Our finding showed the differentially expressed circRNA and mRNA profiles of NSC after radiotherapy, suggesting that circRNA may contribute to the pathogenesis of radiation induced myelopathy.

Uncaria rhynchophylla and Rhynchophylline Inhibit c-Jun N-Terminal Kinase Phosphorylation and Nuclear Factor-κB Activity in Kainic Acid-Treated Rats

2009 ◽  
Vol 37 (02) ◽  
pp. 351-360 ◽  
Author(s):  
Ching-Liang Hsieh ◽  
Tin-Yun Ho ◽  
Shan-Yu Su ◽  
Wan-Yu Lo ◽  
Chung-Hsiang Liu ◽  
...  
Keyword(s):  
Dna Binding ◽  
Kainic Acid ◽  
Epileptic Seizures ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Superoxide Anions ◽  
Sprague Dawley ◽  
Uncaria Rhynchophylla ◽  
Pre Treatment

Our previous studies have shown that Uncaria rhynchophylla (UR) can reduce epileptic seizures. We hypothesized that UR and its major component rhynchophylline (RH), reduce epileptic seizures in rats treated with kainic acid (KA) by inhibiting nuclear factor-κB (NF-κB) and activator-protein-1 (AP-1) activity, and by eliminating superoxide anions. Therefore, the level of superoxide anions and the DNA binding activities of NF-κB and AP-1 were measured. Sprague-Dawley (SD) rats were pre-treated with UR (1.0 g/kg, i.p.), RH (0.25 mg/kg, i.p.), or valproic acid (VA, 250 mg/kg, i.p.) for 3 days and then KA was administered intra-peritoneal (i.p.). The results indicated that UR, RH, and VA can reduce epileptic seizures and the level of superoxide anions in the blood. Furthermore, KA was demonstrated to induce the DNA binding activities of NF-κB and AP-1. However, these inductions were inhibited by pre-treatment with UR, RH, or VA for 3 days. Moreover, UR and RH were shown to be involved in the suppression of c-Jun N-terminal kinase (JNK) phosphorylation. This study suggested that UR and RH have antiepileptic effects in KA-induced seizures and are associated with the regulation of the innate immune system via a reduction in the level of superoxide anions, JNK phosphorylation, and NF-κB activation.

scholarly journals Neuroprotective Effect ofUncaria rhynchophyllain Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Chung-Hsiang Liu ◽  
Yi-Wen Lin ◽  
Nou-Ying Tang ◽  
Hsu-Jan Liu ◽  
Ching-Liang Hsieh
Keyword(s):  
Kainic Acid ◽  
Mossy Fiber ◽  
Neuronal Survival ◽  
Neuroprotective Effect ◽  
Epileptic Seizures ◽  
Cellular Mechanisms ◽  
Mossy Fiber Sprouting ◽  
Astrocyte Proliferation ◽  
Anticonvulsive Effect ◽  
Hippocampal Ca1

Uncaria rhynchophylla(UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABAA) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus

Parthenolide Enhances Cisplatin Sensitivity in Uveal Melanoma by Regulated Mitogen-Activated Protein Kinase Signal Pathway

2021 ◽  
Vol 11 (1) ◽  
pp. 51-58
Author(s):  
Baotong Shu ◽  
Yi Liu ◽  
Yu Ma ◽  
Li Li
Keyword(s):  
Treatment Group ◽  
Protein Kinase ◽  
Cell Line ◽  
Uveal Melanoma ◽  
Cell Activity ◽  
Signal Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Control Group ◽  
Mitogen Activated Protein ◽  
Mapk Signal Pathway

To investigate parthenolide (PTL)’s effect to cisplatin (DDP) sensitivity in uveal melanoma and to show the underlying mechanism. Human uveal melanoma cell line M23 was split into the control group, PTL treatment group, DDP treatment group, PTL + DDP treatment group, DDP + Mitogen-activated protein kinase (MAPK) signal inhibitor (SB203580) treatment group, and PTL + DDP + MAPK signal activator (anisomycin) treatment group. CCK-8 test was conducted to detect cell viability, flow cytometry was utilized for cell apoptosis detection, and western blot was utilized to determine the phosphorylation of p38MAPK and JNK. Compared to the control group, PLT treatment group M23 cell activity, and expression of p-p38MAPK, p-JNK were reduced notably (P < 0.05). Meanwhile, these indices of DDP treatment group were lower than of the control group but higher than of the PTL treatment group. In the PTL + DDP treatment group M23 cell activity and expression level of p-p38MAPK, p-JNK was significantly lower than in the PTL and DDP treatment groups (P < 0.05). Inhibition of MAPK signal pathway increased the DDP effect to proliferation inhibition and apoptosis promotion. In contrast, MAPK signal pathway activator treatment alleviates PTL + DDP treatment effect on M23 cell line apoptosis and proliferation. Parthenolide (PTL) increased cisplatin (DDP) sensitivity in uveal melanoma through the inhibition of MAPK signal pathway.

scholarly journals Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yi-An Lin ◽  
Yan-Rong Li ◽  
Yi-Ching Chang ◽  
Mei-Chich Hsu ◽  
Szu-Tah Chen
Keyword(s):  
Mtor Inhibitor ◽  
Signal Pathway ◽  
C2c12 Cells ◽  
Signal Pathways ◽  
Heavy Chains ◽  
Regenerative Effect ◽  
Ampk Phosphorylation ◽  
Pre Treatment ◽  
Myotube Hypertrophy ◽  
C2c12 Myotube

AbstractThe regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium extract (EE) on skeletal muscle as represented by differentiated C2C12 cells. Here we demonstrated that EE and ICA stimulated C2C12 myotube hypertrophy by activating several, including IGF-1 signal pathways. C2C12 myotube hypertrophy was demonstrated by enlarged myotube and increased myosin heavy chains (MyHCs). In similar to IGF-1, EE/ICA activated key components of the IGF-1 signal pathway, including IGF-1 receptor. Pre-treatment with IGF-1 signal pathway specific inhibitors such as picropodophyllin, LY294002, and rapamycin attenuated EE induced myotube hypertrophy and MyHC isoform overexpression. In a different way, EE induced MHyC-S overexpression can be blocked by AMPK, but not by mTOR inhibitor. On the level of transcription, EE suppressed myostatin and MRF4 expression, but did not suppress atrogenes MAFbx and MuRF1 like IGF-1 did. Differential regulation of MyHC isoform and atrogenes is probably due to inequivalent AKT and AMPK phosphorylation induced by EE and IGF-1. These findings suggest that EE/ICA stimulates pathways partially overlapping with IGF-1 signaling pathway to promote myotube hypertrophy.

scholarly journals SPAK-p38 MAPK signal pathway modulates claudin-18 and barrier function of alveolar epithelium after hyperoxic exposure

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chih-Hao Shen ◽  
Jr-Yu Lin ◽  
Cheng-Yo Lu ◽  
Sung-Sen Yang ◽  
Chung-Kan Peng ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Knockout Mice ◽  
Barrier Function ◽  
Alveolar Epithelium ◽  
Signal Pathway ◽  
Control Group ◽  
Barrier Dysfunction ◽  
Hyperoxic Exposure ◽  
Monolayer Permeability ◽  
Mapk Signal Pathway

Abstract Background Hyperoxia downregulates the tight junction (TJ) proteins of the alveolar epithelium and leads to barrier dysfunction. Previous study has showed that STE20/SPS1-related proline/alanine-rich kinase (SPAK) interferes with the intestinal barrier function in mice. The aim of the present study is to explore the association between SPAK and barrier function in the alveolar epithelium after hyperoxic exposure. Methods Hyperoxic acute lung injury (HALI) was induced by exposing mice to > 99% oxygen for 64 h. The mice were randomly allotted into four groups comprising two control groups and two hyperoxic groups with and without SPAK knockout. Mouse alveolar MLE-12 cells were cultured in control and hyperoxic conditions with or without SPAK knockdown. Transepithelial electric resistance and transwell monolayer permeability were measured for each group. In-cell western assay was used to screen the possible mechanism of p-SPAK being induced by hyperoxia. Results Compared with the control group, SPAK knockout mice had a lower protein level in the bronchoalveolar lavage fluid in HALI, which was correlated with a lower extent of TJ disruption according to transmission electron microscopy. Hyperoxia down-regulated claudin-18 in the alveolar epithelium, which was alleviated in SPAK knockout mice. In MLE-12 cells, hyperoxia up-regulated phosphorylated-SPAK by reactive oxygen species (ROS), which was inhibited by indomethacin. Compared with the control group, SPAK knockdown MLE-12 cells had higher transepithelial electrical resistance and lower transwell monolayer permeability after hyperoxic exposure. The expression of claudin-18 was suppressed by hyperoxia, and down-regulation of SPAK restored the expression of claudin-18. The process of SPAK suppressing the expression of claudin-18 and impairing the barrier function was mediated by p38 mitogen-activated protein kinase (MAPK). Conclusions Hyperoxia up-regulates the SPAK-p38 MAPK signal pathway by ROS, which disrupts the TJ of the alveolar epithelium by suppressing the expression of claudin-18. The down-regulation of SPAK attenuates this process and protects the alveolar epithelium against the barrier dysfunction induced by hyperoxia.

scholarly journals Multimodal in vivo recording using transparent graphene microelectrodes illuminates spatiotemporal seizure dynamics at the microscale

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nicolette Driscoll ◽  
Richard E. Rosch ◽  
Brendan B. Murphy ◽  
Arian Ashourvan ◽  
Ramya Vishnubhotla ◽  
...  
Keyword(s):  
Temporal Resolution ◽  
Spatial Scales ◽  
Epileptic Seizures ◽  
Therapeutic Interventions ◽  
State Transitions ◽  
Integrated Analysis ◽  
High Temporal Resolution ◽  
Seizure Onset ◽  
Acute Seizures

AbstractNeurological disorders such as epilepsy arise from disrupted brain networks. Our capacity to treat these disorders is limited by our inability to map these networks at sufficient temporal and spatial scales to target interventions. Current best techniques either sample broad areas at low temporal resolution (e.g. calcium imaging) or record from discrete regions at high temporal resolution (e.g. electrophysiology). This limitation hampers our ability to understand and intervene in aberrations of network dynamics. Here we present a technique to map the onset and spatiotemporal spread of acute epileptic seizures in vivo by simultaneously recording high bandwidth microelectrocorticography and calcium fluorescence using transparent graphene microelectrode arrays. We integrate dynamic data features from both modalities using non-negative matrix factorization to identify sequential spatiotemporal patterns of seizure onset and evolution, revealing how the temporal progression of ictal electrophysiology is linked to the spatial evolution of the recruited seizure core. This integrated analysis of multimodal data reveals otherwise hidden state transitions in the spatial and temporal progression of acute seizures. The techniques demonstrated here may enable future targeted therapeutic interventions and novel spatially embedded models of local circuit dynamics during seizure onset and evolution.

Functional Role of p38 Mitogen Activated Protein Kinase in Platelet Activation induced by a Thromboxane A2 Analogue and by 8-iso-prostaglandin F2 α

2002 ◽  
Vol 87 (05) ◽  
pp. 888-898 ◽  
Author(s):  
Stefania Gaino ◽  
Valeria Zuliani ◽  
Rosa Tommasoli ◽  
Donatella Benati ◽  
Riccardo Ortolani ◽  
...  
Keyword(s):  
Map Kinase ◽  
Platelet Activation ◽  
Tyrosine Kinases ◽  
Actin Polymerization ◽  
Shape Change ◽  
Specific Inhibitor ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Kinase Phosphorylation

SummaryWe investigated similarities in the signaling pathways elicited by the F2 isoprostane 8-iso-PGF2α and by low doses of U46619 to induce platelet activation. Both 0.01-0.1 µmol/L U46619 and 0.01-1 µmol/L 8-isoPGF2α triggered shape change and filopodia extension, as well as adhesion to immobilized fibrinogen of washed platelets. At these doses the two platelet agonists failed to trigger secretion and aggregation, which were however induced by higher doses of U46619 (0.1-1 µmol/L). SB203580 (1-10 µmol/L), a specific inhibitor of the p38 mitogen activated protein (MAP) kinase blunted platelet shape change and adhesion induced by 0.05-1 µmol/L 8-iso-PGF2α and by 0.01 µmol/L U46619. These platelet responses were also inhibited by 20 µmol/L cytochalasin D, an inhibitor of actin polymerization, and 50 µmol/L piceatannol, an inhibitor of the Syk tyrosine kinases. Both 8-iso-PGF2α and U46619-induced p38 MAP kinase phosphorylation in suspended platelets and this was inhibited by piceatannol, indicating that Syk activation occurs upstream p38 MAP kinase phosphorylation. These findings suggest that the signaling pathway triggered by both 8-iso-PGF2α and low concentrations of U46619 to induce platelet adhesion and shape change implicates Syk, the p38 MAP kinase, and actin polymerization.

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